The aim of this proposal is to continue a multi-faceted research program on induction of uterine cancer with inactivated Herpes simplex virus (HSV) in mice, and to extend studies with this model to other sexually transmitted diseases. Previous studies resulted in the development of premalignant and malignant lesions of the mouse cervix and endometrium after long exposure to inactivated HSV. The present program will explore the cytological, chromosomal, and histological characteristics of these lesions and evaluate the carcinogenic potential of changes that antedate cancer. The carcinogenic potential of certain HSV constituents will also be investigated. These studies will be done with chloroform inactivated virus, complete HSV-DNA, fragmented HSV-DNA, specific HSV-DNA fragments isolated following treatment with restriction endonucleases, and HSV proteins. Studies will be done to determine if integration of viral DNA into the host genome is a part of the carcinogenic process. Southern blot and augmented viral probe techniques will be used to detect the presence of HSV genome or fragments in uterine cancers induced by HSV exposure. Attempts to confer resistance to HSV-induced cervical cancer by immunization of the mice with an HSV vaccine will be continued. In view of the increased frequency of cytomegalovirus and Chlamydia trachomatis infections and the cervical lesions identified with these infections, induction of uterine lesions by methods similar to those of HSV studies will be performed with these agents. These studies will serve to identify the biological agents which may have a role in the genesis of cervical and endometrial cancer.